BackgroundPeste des Petits Ruminants (PPR) is a highly contagious viral disease primarily affecting goats and sheep, with clinical manifestations ranging from peracute disease to subclinical infection, particularly in atypical hosts such as cattle. The role of atypical hosts such as cattle to the spread of PPR remains controversial, with conflicting reports in the literature. Despite its worldwide significance, considerable knowledge gaps exist regarding the pathogenesis and clinical progression in both primary and atypical hosts. This study aimed to elucidate the tissue tropism, pathogenesis, virus shedding, clinical progression, and pathology associated with experimental PPR virus infection in indigenous goats and cattle. To this end, 32 animals—16 goats and 16 cattle—were intranasally inoculated with the Ethiopia/Habru/2014 Lineage-IV strain of the PPR virus followed by detailed clinical evaluations and systematic sampling at pre-established intervals to assess serological conversion, viral shedding, and the pathogenesis of the infection across both species.ResultsThe results show that goats exhibited typical clinical signs 4 days post-inoculation, with seroconversion by day 6 and early detection of viral RNA in swabs and tissues by day 3 and virus isolation starting day 4. In contrast, cattle exhibited minimal clinical signs, with seroconversion occurring at day 8 with viral RNA detected in tissue samples at day 4 and virus isolation starting day 6 in tissues and in a single nasal swab at day 8. Clinical scores and tissue positivity rates significantly differed between goats and cattle (P = 0.007 and P < 0.001, respectively). While goats exhibited expected gross and histopathological lesions, cattle showed only nonspecific lesions.ConclusionsTogether, our findings highlight the importance of comparative pathology studies for better understanding virus dynamics and transmission pathways that may help inform more effective PPR control programs. Future research should explore the pathogenesis of different PPRV lineages in cattle, assessing variations in disease progression and potential for epidemiological impact.