Human activities have significantly impacted natural habitats and wildlife worldwide, particularly emphasizing repercussions for freshwater habitats and associated species. These negative impacts on freshwater fish are well known, but for mammal species that regularly use and dependend on freshwater systems, there is an incomplete understanding. Here, we assessed the status of freshwater and semi-aquatic mammal species inhabiting and dependent on freshwater ecosystems (hereafter referred to as freshwater mammals) and evaluated the impact of human activities on species richness both globally and by biogeographical regions. We used structural equation modeling and simultaneous autoregressive models to assess the direct and indirect effects of seven anthropogenic-related variables on overall freshwater mammal richness. Specifically, we examined the effects of anthropogenic disturbance on the richness of threatened and non-threatened species, as well as species with decreasing and stable/increasing populations. Forty-three percent of all freshwater mammal species are classified as globally threatened by the IUCN Red List, with 50% experiencing population declines. Furthermore, 48% are affected by domestic or international trade, while 75% face threats from geographically expanding human activities. Aridity, pesticide pollution, human footprint, and croplands had the strongest negative effects on freshwater mammal richness. In contrast, the coverage of freshwater habitats (FWs), Indigenous Peoples' lands (IPLs), and protected areas (PAs) helped to sustain freshwater mammal species globally, with an even stronger positive effect at individual biogeographical regions. We conclude that FWs, IPLs, and PAs play a critical role in the conservation of freshwater mammal species, helping safeguard these species from extinction, however, freshwater ecosystems are seldom the focal point of conservation management strategies. The ongoing adverse anthropogenic impacts on these natural habitats present a potentially catastrophic and irreversible threat to global freshwater environments and the species, including humans, reliant upon them. We strongly advocate for the implementation of more robust national and international policy frameworks that endorse alternative and sustainable livelihoods. Such frameworks can play a crucial role in alleviating anthropogenic pressures, thereby aiding in the mitigation of the extinction risk faced by these vital ecosystems and the world's freshwater mammal species.
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