<p>by Maxwell J. Farrell, Samantha K. Tucker, Nardus Mollentze, Daniel G. Streicker</p> A common explanation for bats being a conspicuous source of zoonotic viruses is their purported ability to coexist with viruses without suffering overt disease. Widespread acceptance of the idea that bats have unusual antiviral traits has catalyzed the discovery of unique features of bat immune systems which may have translational value as broad-spectrum antivirals, particularly if they evolved as a byproduct of bats’ unique life history rather than through conventional co-evolutionary processes. Surprisingly, whether bats compared to other host groups suffer less disease from co-evolved viruses or from viruses generally has not been formally assessed. Here, synthesizing 86 years of experimental infections, involving 54 viruses, 85 host species, and over 5,600 animals, we document disease in bats following inoculation by taxonomically diverse viruses, including ones that are relatively benign in humans. The occurrence of overt disease, the likelihood of mortality, and the severity of disease in bats were indistinguishable from those experienced by rodents, another group associated with many zoonotic viruses. These patterns were consistent when considering only bat-associated viruses inoculated into bats and rodent-associated viruses inoculated into rodents and among inoculations which lacked shared co-evolutionary history. Instead, disease outcomes following infection were shaped by experimental design, viral host range, and evolutionary context. Unexceptional disease in bats from novel or co-evolved infections suggests that order-level host life history traits such as flight have inconsistent consequences for antiviral immunity and highlights the need to evaluate the functional properties of putatively unique features of bat immunity in vivo. While these results do not exclude the possibility of developing broader-acting or more potent antivirals from bat immune systems or diminish the potential value of mechanistic insights into bat immunity, they suggest that bat immune systems were shaped by conventional co-evolutionary processes rather than through unique circumstances that endow exceptional antiviral defenses.