Volume 9 ; Issue 2 ; in Month : July-Dec (2026) Article No : 180
Kumar S, Karim MJ, Fazal B, et al.

Abstract

Large mammals represent a valuable yet comparatively underexplored source of biological information for understanding the mechanisms that determine disease resistance, disease tolerance, immune-mediated tissue injury, and survival. Unlike conventional laboratory models, large mammals exhibit distinctive physiological, immunological, metabolic, and evolutionary adaptations that can substantially influence host–pathogen interactions. This review provides a comprehensive comparative perspective on the biological mechanisms underlying lethal disease in large mammals, with particular emphasis on the interaction between pathogen virulence, innate and adaptive immunity, inflammatory signalling, cellular stress, regulated cell death, tissue injury, and systemic organ dysfunction. Major disease models, including bovine leukemia virus, African swine fever, bovine respiratory disease, chronic wasting disease, foot-and-mouth disease, hemorrhagic septicemia, and bovine tuberculosis, are considered to illustrate distinct patterns of persistent infection, acute systemic inflammation, immune evasion, immunosuppression, neurodegeneration, and immunopathology. The review further examines species-specific immune adaptations, highlighting elephants as models of enhanced tumour surveillance, camelids as unique sources of heavy-chain-only antibodies and nanobody technologies, and bats as important models for understanding antiviral resistance and disease tolerance. Particular emphasis is placed on the emerging concept that survival depends not only on pathogen elimination but also on the ability of the host to limit collateral tissue damage during infection. Collectively, comparative immunology of large mammals provides an evolution-inspired framework for discovering mechanisms of disease resistance and tolerance and translating naturally evolved biological solutions into innovative strategies for infectious disease, inflammatory disorders, and cancer research.

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