Distinct host-pathogen and microbiome responses of aoudad (Ammotragus lervia) and bighorn sheep (Ovis canadensis) following exposure to Mycoplasma ovipneumoniae

Background: Pathogens can shape their host communities over various timescales. The potential role of host-pathogen coevolution in driving contemporary shifts in disease ecology is becoming increasingly important as host species emerge and persist outside their native ranges. In North America, Mycoplasma ovipneumoniae can cause fatal pneumonia epizootics in native bighorn sheep ( Ovis canadensis ), whereas introduced free-ranging sympatric aoudad ( Ammotragus lervia ) typically act as asymptomatic reservoirs. To elucidate the role of host–pathogen coevolution in shaping these observed patterns of host impacts, we integrated findings on microbiome composition and host transcriptomic responses in aoudad and bighorn sheep following controlled exposure to M. ovipneumoniae , with or without leukotoxigenic Pasteurellaceae. Results: Aoudad maintained significantly higher microbial richness (Chao1) and evenness (Shannon index) across tonsillar swabs and lower respiratory tract samples, whereas bighorn sheep experienced microbiome perturbations and enhanced growth of some opportunistic taxa. Exposure to M. ovipneumoniae reduced the relative abundance of key commensal genera (e.g., Bibersteinia , Mannheimia , Pasteurella , Roseomonas ) and enriched Mycoplasma in both hosts, but bacterial community destabilization was more pronounced in bighorn sheep. Transcriptome profiling revealed that bighorn sheep upregulated pro-inflammatory and oxidative-stress pathways—including interleukin-1, interleukin-12, and NF-κB signaling—alongside reactive oxygen species generation. In contrast, aoudad exhibited comparatively muted inflammatory signatures, enhanced expression of molecular chaperones, antigen-processing machinery, and integrin-mediated regulatory genes (notably CD46, ILK, and NFKBIZ). Network analysis identified distinct hub genes likely underpinning effective pathogen clearance and mucosal resilience in aoudad versus immunopathology in bighorn sheep. Conclusions: Our integrated microbiome and transcriptomic data underscore the importance if coevolutionary history in driving host-specific responses to shared respiratory pathogens. Aoudad display microbiome stability and balanced immunoregulation, whereas bighorn sheep suffer dysbiosis and excessive inflammation, potentially increasing mortality risk. Incorporating evolutionary and ecological context into managing disease interfaces requires a direct understanding of host-pathogen interactions, as well as how these interactions create observed pathobiological and epidemiological patterns commonly targeted for disease management interventions.