Published in last 50 years
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Articles published on Peromyscus Leucopus
- Research Article
- 10.1111/1365-2656.70143
- Sep 28, 2025
- The Journal of animal ecology
- Elise F Zipkin + 1 more
Research Highlight: Dri, G. F., Bogdziewicz, M., Hunter, M., Witham, J., & Mortelliti, A. (2025). Coupled effects of forest growth and climate change on small mammal abundance and body weight: Results of a 39-year field study. Journal of Animal Ecology. https://doi.org/10.1111/1365-2656.70114. Biodiversity is declining due to global environmental change, yet it remains challenging to assess how specific drivers, such as climate change, affect the dynamics and trends of individual species. While many studies correlate climate variables with species abundance or occurrence, few explicitly link environmental drivers to demographic processes to uncover the mechanisms behind population trends. Such insight requires long-term data capable of revealing slow-moving, nonlinear trends and disentangling natural variability from directional change. In a 39-year study, Dri etal. (2025) demonstrate the power of sustained observation and mechanistic approaches by linking climate warming and forest maturation to increased acorn production, which enhanced body condition and survival in white-footed mice, ultimately driving population increases. Their findings underscore the importance of long-term data for identifying meaningful ecological trends and tracing the causal pathways by which biodiversity changes. Effective conservation under global change depends on two key shifts: greater investment in long-term biodiversity monitoring and broader adoption of frameworks that explicitly connect environmental drivers to demographic responses. Together, these approaches provide the foundation for adaptive, evidence-based conservation strategies in a rapidly changing world.
- Research Article
- 10.21203/rs.3.rs-7312978/v1
- Sep 10, 2025
- Research Square
- Karen C Poh + 3 more
Ixodes scapularis is considered a significant medical and veterinary arthropod pest, capable of transmitting several pathogens that cause disease in humans and animals. Previous work has identified two distinct populations of I. scapularis in the United States (northern and southern), characterized by differences in their genetics and behavior. This study aimed to characterize and compare the lateral movement and feeding behaviors of nymphal I. scapularis between the northern and southern populations in the United States. Using laboratory-reared ticks from BEI (northern), Oklahoma State University (southern), and field-collected ticks from central Pennsylvania (Mid-Atlantic), behavioral bioassays were conducted to quantify distances traveled and velocities in a one-hour time frame. Ticks from the northern lineage walked longer distances and at faster speeds compared to ticks from the southern lineage. Field-collected ticks from central Pennsylvania, located between what is considered the northern and southern populations, exhibited similar movement behaviors as ticks from the southern population, even though ticks from the Mid-Atlantic are geographically categorized as the northern population. To compare feeding behaviors, colony-reared white-footed mice (Peromyscus leucopus) were artificially infested with northern and southern ticks, and the percentages of infestation and feeding successes were compared. Northern ticks had higher success in infestations and feeding to repletion compared to southern ticks. These behavioral differences in movement and feeding patterns provide additional evidence for the hypothesis that geographically distinct populations of I. scapularis exist across the United States. Researchers should consider these population differences when selecting tick lineages for behavioral studies and other blacklegged tick research.
- Research Article
- 10.1128/iai.00246-25
- Sep 3, 2025
- Infection and Immunity
- Elis A Fisk + 6 more
Ticks are obligate hematophagous parasites and pathogen vectors responsible for morbidity and mortality worldwide. Ixodes scapularis is a vector for at least seven pathogens relevant to human and animal health, including the Lyme disease microbe, Borrelia burgdorferi, and the causative agent of anaplasmosis, Anaplasma phagocytophilum. Tick-host interactions affect the maintenance of tick-borne pathogens in a population. Here, we report that repeated I. scapularis larval infestations on the wild host species Peromyscus leucopus lead to immune-mediated rejection of the tick, a phenomenon termed acquired tick resistance (ATR). On previously infested mice, we observed that larval feeding success was reduced by over 50%, and fed larvae had decreased blood meal weights compared to larvae fed on naïve hosts. Over sequential infestations, mice exhibited increasingly severe inflammation at tick bite sites characterized by an influx of basophils, eosinophils, neutrophils, and T lymphocytes. Larvae fed on sensitized mice ingested higher quantities of host leukocytes when compared to ticks fed on naïve hosts, which rarely ingested nucleated cells. When challenged with B. burgdorferi or A. phagocytophilum, larvae fed on sensitized mice ingested more bacteria. Altogether, we demonstrate that reservoir host species develop ATR against larval I. scapularis, which reduces tick feeding success and affects pathogen ingestion by larvae. These results indicate that ATR could impact Ixodes population dynamics, prevalence of infected ticks, and pathogen circulation in the wild.
- Research Article
- 10.1002/ece3.72038
- Aug 22, 2025
- Ecology and Evolution
- Mark E Fuka + 2 more
ABSTRACTChanges in the global environment are widespread and may have unappreciated effects on the activity of animals and the strength of animal‐mediated interactions. For example, urbanization and the spread of invasive species are aspects of global change that may lead to shifts in the activity of granivorous rodents, potentially leading to changes in the survival and establishment of seeds rodents consume. Importantly, these two aspects of global change could interact to affect rodent activity. We used a large‐scale manipulation of common invasive shrubs (Rhamnus cathartica, Lonicera macckii) across a rural‐to‐urban forest gradient spanning southern Wisconsin in summer and autumn to examine the effects that urbanization, invasion, and seasonality had on modifying rodent activity and granivory. Using two 14‐day sampling sessions, we recorded the activity of three granivorous rodents (Peromyscus leucopus, Sciurus carolinensis, and Tamias striatus) with motion‐activated cameras and quantified seed removal using six tree species (Quercus rubra, Quercus alba, Acer saccharum, Prunus serotina, Pinus strobus, and Pinus resinosa) with seed depots to link animal activity with seed removal. Our findings reveal that Quercus seed removal was highest in urban sites, potentially linking hotspots of S. carolinensis activity in urban forests to decreased seed survival. In capturing a large number of P. leucopus photos during the autumn in R. cathartica removed plots, our findings suggest that P. leucopus may be responding to the provision of short‐term resources. Our results underscore the primacy of seed mass in determining rodent seed choice: although urbanization and invasive shrubs had different effects on the activity of rodent species, the removal of seeds was always strongly dependent upon seed mass. Our findings help to illuminate potential hotspots of granivorous rodent activity along an urbanization gradient, the shifts in species‐specific seed loss associated with this gradient, and the dominance of seed mass in contributing to rodent seed preference.
- Research Article
- 10.1111/1365-2656.70114
- Aug 21, 2025
- The Journal of animal ecology
- Gabriela Franzoi Dri + 4 more
In rapidly changing environments, the combined effects of climate change and forest stand changes-such as growth or regeneration-are altering the availability of resources, particularly in systems with pulsed resources like seed-masting. These environmental shifts can have cascading impacts on animal populations, ultimately reshaping ecosystem structure and function. However, relevant studies are rare as they require long-term monitoring of both seed supply and animal populations. We investigated how temporal changes in resource availability (red oak acorns [Quercus rubra]) influence the demographics and physical traits of white-footed mice (Peromyscus leucopus) using a 39-year dataset from Maine, USA, which includes: mouse abundance and body weight, red oak tree size and acorn production, and seasonal temperatures. Our analysis of 5032 individual mice revealed a significant increase in both abundance (by 67%) and average body weight (by 15%) over four decades. We found that oaks produced more acorns as they grew, while warmer spring temperatures led to larger crops. This indicates that both forest growth and climate change have driven the increase in resource availability. The increase in acorn production was translated into higher mouse abundance and body weight. Notably, heavier mice also showed a higher probability of survival. These results demonstrate that changes in food supply, driven by the combined effects of forest growth and climate change, have significant effects on animal population dynamics. Furthermore, given the important role of white-footed mice as seed predators and dispersers, and disease vectors, these shifts have far-reaching implications for the ecosystem.
- Research Article
- 10.1016/j.meegid.2025.105767
- Aug 1, 2025
- Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
- Spenser J Babb-Biernacki + 8 more
Three distinct forms of Pneumocystis coexist in individuals of two species of deer mice (genus Peromyscus).
- Research Article
- 10.1101/2025.07.16.665222
- Jul 18, 2025
- bioRxiv
- Jonathan V Duong + 5 more
The white-footed deermouse Peromyscus leucopus is a primary reservoir for the agents of Lyme disease and other zoonoses in North America and manifests infection tolerance for the bacteria, protozoa, and viruses it hosts. In previous in vivo studies P. leucopus and M. musculus differed in the degree of sickness and profiles of biomarkers after exposure to bacterial lipopolysaccharide, a TLR4 agonist. As an approach for assessing immunity of mammals in nature and for longitudinal studies of colony animals in the laboratory, we evaluated using bulk and single cell RNA-seq primary dermal fibroblast cultures of P. leucopus and M. musculus in their short-term responses to a TLR2 agonist lipopeptide. By single cell RNA-seq cultures of both species comprised at least two types of fibroblasts, which were further differentiated in their responses to TLR agonists. With continued passage the mouse cell population lost viability, while the deermouse cell population spontaneously transformed into a cell line stably maintained under standard conditions. Bulk RNA-seq revealed distinctive profiles for deermouse and mouse cells in arginine metabolism gene expression, high baseline transcription of the antioxidant transcription factor Nfe2l2 (Nrf2) in deermouse fibroblasts, and the transcription of the aging-associated cytokine interleukin-11 in agonist-treated mouse fibroblasts but not deermouse fibroblasts. In both species' cultures there was increased transcription of several types of endogenous retrovirus (ERV) and transposable elements (TE) after exposure to the agonist. The transcribed ERV/TE sequences in M. musculus cells were generally longer in length and with greater potential for translation than sequences in treated P. leucopus cells. The results indicate feasibility of this in vitro model for both laboratory- and field-based studies and that inherent differences between deermice and mice in cell-autonomous innate immune responses and ERV/TE activation can be demonstrated in dermal fibroblasts as well as the animals themselves.
- Research Article
- 10.1093/infdis/jiaf363
- Jul 4, 2025
- The Journal of infectious diseases
- Stephanie S You + 7 more
Lyme disease spirochetes are maintained in natural reservoirs before spilling over into human populations. Targeting these reservoirs with vaccinations or antibiotics could impact the B. burgdorferi enzootic cycle and reduce the risk of human Lyme disease. In this work we report that the narrow spectrum antibiotic hygromycin A is sufficient to disrupt B. burgdorferi transmission from the main eastern U.S. reservoir, Peromyscus leucopus, to ticks. Additionally, hygromycin A-containing baits can clear B. burgdorferi from P. leucopus. These studies lay the foundation for the use of hygromycin A as a reservoir-targeted antibiotic to eradicate B. burgdorferi in the wild.
- Research Article
- 10.3201/eid3107.241579
- Jul 1, 2025
- Emerging infectious diseases
- Ellie J Putz + 9 more
Leptospirosis is a global zoonotic disease affecting humans, wildlife, companion, and domestic animals. Incidental hosts can contract the disease directly or indirectly from asymptomatic reservoir hosts, most commonly small rodents. The Golden Syrian hamster is recognized as the dominant rodent model for acute leptospirosis because the animals are susceptible to many serovars and are used to maintain laboratory strains and test bacterin vaccine efficacy. However, hamsters are primarily used in survival-based studies, and investigations into host immune response and disease pathogenesis are limited. We found that Peromyscus leucopus white-footed deer mice are susceptible to acute leptospirosis, and thus might be an alternative rodent model. Furthermore, similar to hamsters, deer mice produce circulating foamy macrophages in response to Leptospira challenge. Deer mice exhibit differences in response to different serovars, clinical disease severity, kidney and liver lesions, and an overall sex effect, with male mice demonstrating more severe clinical signs and higher bacterial burden.
- Research Article
- 10.1242/jeb.249797
- Jun 20, 2025
- The Journal of experimental biology
- Kevin D Kohl + 12 more
To efficiently digest food resources that may vary spatially and temporally, animals maintain physiological flexibility across levels of organization. For example, in response to dietary shifts, animals may exhibit changes in the expression of digestive enzymes, the size of digestive organs or the structure of their gut microbiome. A 'Grand Challenge' in comparative physiology is to understand how components of flexibility across organizational levels may scale to cumulatively determine organismal performance. Here, we conducted feeding trials on three rodent species with disparate feeding strategies: herbivorous montane voles (Microtus montanus), omnivorous white-footed mice (Peromyscus leucopus) and carnivorous grasshopper mice (Onychomys torridus). For each species, four groups of individuals were presented with diets that varied in carbohydrate, fiber and protein content. After 4-5 weeks, we measured organismal performance in the form of nutrient digestibility (dry matter, nitrogen, fiber). We also measured gut anatomy and organ size, and conducted enzyme assays on various tissues to measure activities of carbohydrases and peptidases. We found some shared physiological responses, e.g. fiber generally increased gut size across species. However, the specifics of these responses were distinct across species, suggesting different capacities for flexibility. Thus, in the context of digestion, we still lack an understanding of how flexibility across organizational levels may scale to determine whole-animal performance.
- Research Article
1
- 10.1242/jeb.249794
- Jun 18, 2025
- The Journal of experimental biology
- Nick Barts + 5 more
Diet and host identity play fundamental roles in digestive physiology and the assembly of gut microbial communities. Research shows that microbial communities are plastic, with abundances of taxa and community interactions exhibiting changes in response to diet. Few studies considering the influence of diet on host and microbial plasticity disentangle the unique roles of specific nutrients, such as protein and fiber. Additionally, in the context of host-microbiome interactions, few studies have explored how host dietary strategies shape the plastic responses of microbial communities within the host digestive tract. To address these current gaps, we fed rodents with distinct dietary strategies (Peromyscus leucopus, Microtus montanus and Onychomys torridus) diets varying in fiber and protein content. Species varied in the degree of cecum size plasticity, with the carnivore showing no significant changes and the omnivore responding to both fiber and protein manipulation. There were also differences in the diversity indices of bacterial and fungal communities across hosts, and the microbes driving those differences were largely unique across rodent species. Additionally, community network interactions varied across treatments, and hub taxa that play a role in regulating network properties were identified. For example, bacteria in the Eubacterium groups, which are known to aid in fiber fermentation, were identified as hub taxa in all three species, but no group shared the same Eubacterium as a hub taxa. Overall, our data suggest that hosts with unique dietary strategies and their microbiomes respond uniquely to changes in the nutrient composition of their diets.
- Research Article
- 10.1121/10.0036945
- Jun 1, 2025
- The Journal of the Acoustical Society of America
- Luberson Joseph + 7 more
The genus Peromyscus has been extensively used as a model for ecological, behavioral, and evolutionary studies. This study used auditory brainstem responses (ABRs), craniofacial morphology, and pinna measurements to compare two wild-caught species, Peromyscus leucopus and Peromyscus maniculatus. It was observed that P. leucopus exhibited larger features and bigger overall size compared to P. maniculatus. ABR recordings showed similar hearing thresholds with peak sensitivity between 8 and 46 kHz for both species. There were no significant differences between species for absolute amplitudes of waves IV and I, with significantly higher amplitude ratio of wave IV to wave I in P. leucopus across intensities. There were also species differences (faster wave I in P. maniculatus) and sex differences (faster wave I in female P. leucopus) for absolute latency, which were no longer significant when considering inter-peak latency between waves I and IV. Finally, faster normalized latencies of the binaural interaction component (BIC) were observed in P. maniculatus, while no differences were observed across relative BIC amplitude between species. These results provide additional ABR related data that expand the use of both Peromyscus species as future models for auditory research.
- Research Article
- 10.1128/iai.00581-24
- May 27, 2025
- Infection and immunity
- Christopher C Wells + 6 more
Currently, most tools utilized in host-pathogen interaction studies depend on the use of human or mouse (Mus musculus) cells and tissues. While these species have led to countless breakthroughs in our understanding of infectious disease, there are undoubtedly important biological processes that are missed by limiting studies to these two vertebrate species. For instance, it is well-established that a common deermouse in North America, Peromyscus leucopus, has unique interactions with microbes, which likely shape its ability to serve as a critical reservoir for numerous zoonotic pathogens, including a Lyme disease spirochete, Borrelia burgdorferi. In this work, we expand the immunological toolkit to study P. leucopus biology by performing the first differentiation of deermouse bone marrow to macrophages using P. leucopus M-CSF producing HEK293T cells. We find that P. leucopus BMDMs generated through this method behave broadly very similarly to C57BL/6J macrophages generated with the L-929 supernatant, although RNA sequencing revealed modest differences in transcriptomic responses to B. burgdorferi and lipopolysaccharide. In particular, differences in Il-10 induction and caspase expression were observed between the species.
- Research Article
- 10.1128/iai.00216-25
- May 19, 2025
- Infection and Immunity
- Jose F Azevedo + 4 more
The efficacy and duration of passive immunity protection depend on maternal antibody levels and transfer efficiency. We investigated whether oral vaccination of Peromyscus leucopus dams with recombinant outer surface protein A (OspA)-expressing Escherichia coli could induce maternal transfer of anti-OspA antibodies and protect pups from Borrelia burgdorferi challenge. Dams were vaccinated until breeding pairs were created (i), until parturition (ii), and until pups were 2 weeks old (iii). Pups were challenged with nymphal Ixodes scapularis-transmitted B. burgdorferi at ~4 weeks of age. Anti-OspA IgG was quantified in dams and pups, and anti-B. burgdorferi IgG was quantified in pups. B. burgdorferi burden was assessed by flaB quantitative PCR in pups' tissues ~4 weeks after tick challenge, and viability of B. burgdorferi was assessed by culture of the heart tissue. P. leucopus pups born to dams vaccinated until breeding had low serologic anti-OspA antibody and were not protected from tick-transmitted B. burgdorferi infection. However, when dams' vaccination extended until parturition and until pups were 2 weeks old, significant anti-OspA antibody transfer and protection from B. burgdorferi infection occurred. This was evidenced by the absence of antibody to B. burgdorferi PepVF, absence of B. burgdorferi flaB DNA in heart and bladder tissues, and absence of flaB in culture from heart tissues from pups euthanized >9 weeks after birth. We show that the transfer of anti-OspA antibodies from vaccinated P. leucopus dams to offspring prevents tick transmission and infection dynamics of B. burgdorferi in the major reservoir host of this spirochete in the USA.IMPORTANCEThis study contributes to our understanding of how interventions based in reservoir-targeted outer surface protein A vaccines designed to block transmission of B. burgdorferi from infected Ixodes scapularis ticks may disrupt the enzootic cycle of this spirochete and reduce incidence of Lyme disease.
- Research Article
- 10.1111/jzo.70010
- May 7, 2025
- Journal of zoology (London, England : 1987)
- Jessica E Brown + 2 more
The presence of parasites can significantly influence animal behavior. Specifically, grooming behavior may have evolved in part as a response to the physical and psychological challenges induced by parasitism. Grooming behaviors, which can be individual or social, help remove parasites, maintain hygiene, and offer stress relief. These interactions underscore the adaptive coping strategies of animals for environmental challenges, highlighting the role of parasites in shaping animal behavior and survival. A continual rise in human cases of vector-borne disease demands a more detailed understanding of how ticks interact with their host species that usually serve as pathogen reservoirs. White-footed mice (Peromyscus leucopus) are one of the most frequently studied hosts of blacklegged ticks (Ixodes scapularis); however, interactions between white-footed mice and ticks are not easily observed. This study aimed to quantify activity patterns in white-footed mice and to assess their behavioral responses to parasitism by blacklegged ticks within a controlled setting using Ethovision® software. White-footed mice were infested with nymphal blacklegged ticks or evaluated without tick infestation over 4 days. The mean number of ticks on the mice after the infestation period was 19.6 ± 5.9, and the mean number of ticks that attached and fed through the duration of the trial on the infested mice out of these was 8.6 ± 4.4. Grooming frequency was not significantly affected by tick parasitism, regardless of the number of attached ticks. While this study was the first to quantify behavior on lab-reared white-footed mice in response to blacklegged tick parasitism, further work is needed to determine how wild-caught white-footed mouse behavior might differ.
- Research Article
- 10.1096/fba.2024-00115
- Apr 17, 2025
- FASEB bioAdvances
- Margaret E Newport + 6 more
Physiology is closely synchronized to daily and seasonal light/dark cycles. Humans artificially extend daylight and experience irregular light schedules, resulting in dysregulation of metabolism and body mass. In rodents, winter-like conditions (cold and short photoperiod) can alter energy balance and adipose tissue mass. To determine if photoperiod alone, independent of temperature, is a strong enough signal to regulate adiposity, we compared the effects of long and short photoperiod at thermoneutrality on adiposity and WAT gene expression in photoperiod-sensitive, F1 generation wild-derived adult male white-footed mice (Peromyscus leucopus). Mice were housed in long-day (16:8 light:dark) or short-day (8:16 light:dark) photoperiod conditions at thermoneutrality (27°C) for 4 weeks with the extended light being provided through artificial lighting. Photoperiod did not impact body weight or calorie consumption. However, mice housed in long photoperiod with extended artificial light selectively developed greater visceral WAT mass without changing subcutaneous WAT or interscapular BAT mass. This was accompanied by a decrease in Adrβ3 and Ucp1 mRNA expression in visceral WAT with no change in Pgc1a, Lpl, or Hsl. Expression of Per1, Per2, and Nr1d1 mRNA in visceral WAT differed between long and short photoperiods over time when aligned to circadian time but not onset of darkness, indicating alterations in clock gene expression with photoperiod. These findings suggest that extended photoperiod through artificial light can promote visceral fat accumulation alone, independent of temperature, supporting that artificial light may play a role in obesity.
- Research Article
- 10.3390/microorganisms13040888
- Apr 12, 2025
- Microorganisms
- Robert Jory Brinkerhoff + 4 more
Host microbiota may impact disease vector behavior and pathogen transmission, but little is known about associations between ectoparasites and microbial communities in wildlife reservoir species. We used Illumina metagenomic sequencing to explore the impacts of tick parasitism on the rodent fecal microbiome in both a field and laboratory setting. We found that tick parasitism on wild hosts was associated with variation in the fecal microbiota of both the white-footed deermouse, Peromyscus leucopus, and the southern cotton rat, Sigmodon hispidus. In a lab experiment, we detected significant changes to the fecal microbiome after experimental exposure to immature ticks in treated versus control BALB/c mice. Whereas there is variation in the fecal microbiome associated with each of the host species we tested, some of the same microbial taxa, notably members of the family Muribaculaceae, occurred at higher relative abundance in tick-parasitized hosts in both the field and laboratory studies, suggesting that there are consistent impacts of tick parasitism on the host gut microbiome. We recommend future studies to test the hypothesis that epithelial cell secretions, generated as part of the host's immune response to tick parasitism, could provide resources that allow particular microbial lineages in the mammalian gut to flourish.
- Research Article
- 10.1016/j.ijppaw.2025.101054
- Apr 1, 2025
- International journal for parasitology. Parasites and wildlife
- Gabriel P Andrade-Ponce + 4 more
Different drivers, same tick: Effect of host traits, habitat, and climate on the infestation of three rodent species by larval D ermacentor ticks.
- Research Article
- 10.1093/gbe/evaf048
- Mar 20, 2025
- Genome biology and evolution
- Emma K Howell + 2 more
Contemporary patterns of genetic variation reflect the cumulative history of a population. Population splitting, migration, and changes in population size leave genomic signals that enable their characterization. Existing methods aimed at reconstructing these features of demographic history are often restricted in their temporal resolution, leaving gaps about how basic evolutionary parameters change over time. To illustrate the prospects for extracting insights about dynamic population histories, we turn to a system that has undergone dramatic changes on both geological and contemporary timescales-an urbanized, near-shore archipelago. Using whole genome sequences, we employed both common and novel summaries of variation to infer the demographic history of three populations of endemic white-footed mice (Peromyscus leucopus) in Massachusetts' Boston Harbor. We find informative contrasts among the inferences drawn from these distinct patterns of diversity. While demographic models that fit the joint site frequency spectrum (jSFS) coincide with the known geological history of the Boston Harbor, patterns of linkage disequilibrium reveal collapses in population size on contemporary timescales that are not recovered by our jSFS-derived models. Historical migration between populations is also absent from best-fitting models for the jSFS, but rare variants show unusual clustering along the genome within individual mice, a novel pattern that is reproduced by simulations of recent migration. Together, our findings indicate that these urban archipelago populations have been shaped by both ancient geological processes and recent human influence. More broadly, our study demonstrates that the temporal resolution of demographic history can be extended by examining multiple facets of genomic variation.
- Research Article
- 10.1128/iai.00065-25
- Mar 11, 2025
- Infection and immunity
- Jeffrey S Bourgeois + 11 more
Ixodes scapularis ticks are an important vector for at least seven tick-borne human pathogens, including a North American Lyme disease spirochete, Borrelia burgdorferi. The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without triggering an immune response capable of preventing tick feeding. While the ability of nymphal ticks to feed on a variety of hosts has been well documented, the host-parasite interactions between larval I. scapularis and different vertebrate hosts are relatively unexplored. Here we report on the changes in the vertebrate host transcriptome present at the larval tick bite site using the natural I. scapularis host Peromyscus leucopus, a non-natural rodent host, Mus musculus (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in P. leucopus compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite sites. We also note that bite sites on BALB/c mice and humans, but not deer mice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval I. scapularis and P. leucopus and, in addition, expand our overall understanding of I. scapularis feeding.