Comparative Susceptibility to PM2.5-Induced Pulmonary Pathology: A Lifespan-Based Perspective on Animal Models

Fine particulate matter (PM2.5) is a leading environmental cause of respiratory disease, yet most evidence for its pulmonary toxicity comes from short-lifespan laboratory rodents exposed at high concentrations for a small fraction of their lives. The chemically heterogeneous components of PM2.5 converge on shared innate and adaptive inflammatory pathways across species. Whether these findings describe the disease that develops in long-lived animals breathing ambient air across decades remains unresolved. This review contrasts the phenotypic, cellular, and temporal manifestations of PM2.5-induced lung disease between short- and long-lifespan animals, across anatomical and physiological variables, time at risk, and immune response kinetics. Short-lifespan models express an acute, frequently reversible inflammatory injury, whereas long-lifespan species express a chronic phenotype of cumulative particle bioaccumulation, airway remodeling, and spontaneously arising neoplasia. These poles are not mutually exclusive: sufficient dose or observation time can drive short-lived models into the chronic phenotype, and lifespan remains confounded with exposure design, so it cannot yet be separated from exposure intensity and duration. The two groups are therefore best viewed as complementary, rather than competing, sources of evidence. Within a One Health framework, future priorities include long-term veterinary sentinel cohorts in high-exposure regions, cross-species dosimetric scaling, and direct in-tissue quantification of retained particle burden to link dose to lesion.