Variability in infection dynamics emerges from the interplay between unique host and pathogen characteristics.

Variation in infection dynamics across host species can profoundly influence parasite epidemiology, ecology, and evolution. However, because experiments involving multiple hosts and multiple parasite species that capture the full infection dynamics within hosts are rare, the underlying mechanisms of host heterogeneity effects across different parasite species remain largely unknown. We dissected the specific roles of host and pathogen effects in shaping within-host infection dynamics using a model system comprising three coexisting rodent species from Israel's northwestern Negev Desert and their predominant bacterial pathogens, Bartonella krasnovii A2 and Mycoplasma haemomuris-like bacterium. To test whether the effects of host species heterogeneity on parasite dynamics mainly derive from host trait variation ("host trait variation hypothesis") or rather reflect a unique host-parasite interaction ("specific host-parasite interaction" hypotheses), we inoculated rodents of the three species (Gerbillus andersoni, G. pyramidum, and G. gerbillus) with either Bartonella or Mycoplasma and compared their infection dynamics during primary infection and upon reinfection. According to the "host trait variation" hypothesis, host heterogeneity effects would be consistent across parasite species. Supporting this hypothesis, both bacterial pathogens exhibited reduced performance in G. gerbillus compared to the other rodent species. However, consistent with the alternative "specific host-parasite interaction" hypothesis, all other aspects of the infection dynamics of these two pathogens exhibited varying trends across the three hosts, indicating the uniqueness of each pathogen-host interaction. Our findings support the notion that the variability in infection dynamics is not solely attributable to host heterogeneity, but rather emerges from the interplay between specific host characteristics and parasite traits. We discuss potential directions for future research to deepen our understanding of within-host dynamics in multispecies communities. We stress the necessity of analyzing each distinct host-parasite interaction independently when making inferences about community patterns based on infection dynamics within hosts until more experimental data on natural systems are accumulated.