Distinct host–pathogen and microbiome responses of aoudad (Ammotragus lervia) and bighorn sheep (Ovis canadensis) following exposure to Mycoplasma ovipneumoniae with or without co-exposure to leukotoxigenic Pasteurellaceae

Pathogens can shape their host communities over various timescales. The potential role of host–pathogen co-evolution 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. We describe the responses of two hosts with different biogeographical histories to shared pathogen exposure through a lens of potential host–pathogen co-evolution. Specifically, this work integrates findings on microbiome composition and host transcriptomic responses in aoudad and bighorn sheep before and after controlled exposure to M. ovipneumoniae, with or without leukotoxigenic Pasteurellaceae. Aoudad maintained significantly higher microbial richness (Shannon) in the lower respiratory tract, whereas bighorn sheep experienced post-exposure microbiome perturbations and enhanced growth of some opportunistic taxa. Both molecular detection of and humoral antibodies to M. ovipneumoniae reduced the relative abundance of key genera (e.g., Bibersteinia, Mannheimia, Pasteurella, Roseomonas) in the upper respiratory tract, but post-exposure bacterial community alteration was more pronounced in bighorn sheep. Transcriptome profiling revealed that, compared to aoudad, 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. Our integrated microbiome and transcriptomic data underscore the importance of co-evolutionary 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. Explicit consideration of evolutionary and ecological context regarding host–pathogen co-evolution may increase overall understanding of observed pathobiological and epidemiological patterns commonly targeted for disease management interventions.