Host immune responses to enzootic and invasive pathogen lineages vary in magnitude, timing, and efficacy

Infectious diseases of wildlife continue to pose a threat to biodiversity worldwide, yet pathogens are far from monolithic in virulence. Within the same pathogen species, virulence can vary considerably depending on strain or lineage, in turn eliciting variable host responses. One pathogen that has caused extensive biodiversity loss is the amphibian-killing fungus, Batrachochytrium dendrobatidis (Bd), which is comprised of a globally widespread hypervirulent lineage (Bd-GPL), and multiple geographically restricted lineages. Whereas host immunogenomic responses to Bd-GPL have been characterized in a number of amphibian species, immunogenomic responses to geographically-restricted, enzootic Bd lineages are unknown. To examine lineage-specific host immune responses to Bd, we exposed a species of pumpkin toadlet, Brachycephalus pitanga, which is endemic to Brazil's Southern Atlantic Forest, to either the Bd-GPL or the enzootic Bd-Asia-2/Brazil (hereafter Bd-Brazil) lineage. We quantified functional immunogenomic responses over the course of infection using differential gene expression tests and coexpression network analyses. Host immune responses varied significantly with Bd lineage. Toadlet responses to Bd-Brazil were weak at early infection (26 genes differentially expressed), peaked by mid-stage infection (435 genes) and were nearly fully resolved by late-stage disease (9 genes). In contrast, responses to Bd-GPL were magnified and delayed; toadlets differentially expressed 97 genes early, 86 genes at mid-stage infection, and 728 genes by late-stage infection. Given that infection intensity did not vary between mid- and late-stage disease, this suggests that pumpkin toadlets may be at least partially tolerant to the geographically-restricted Bd-Brazil lineage. In contrast, mortality was higher in Bd-GPL-infected toadlets, suggesting that late-stage immune activation against Bd-GPL was not protective and was consistent with immune dysregulation previously observed in other species. Our results demonstrate that both the timing of immune response and the particular immune pathways activated are specific to Bd lineage. Within regions where multiple Bd lineages co-occur, and given continued global Bd movement, these differential host responses may influence not only individual disease outcome, but transmission dynamics at the population and community levels. ### Competing Interest Statement The authors have declared no competing interest.