Serum proteomic profiling reveals immune and inflammatory mechanisms driving susceptibility to buffalo fly-induced skin lesions in cattle

Buffalo fly (Haematobia irritans exigua) infestation in cattle poses a significant challenge to animal health and welfare, causing blood loss and often painful skin lesions. These lesions can reduce the value of cattle in saleyards, make cattle unacceptable for certain markets, and provide a focus for secondary infections; yet, the underlying mechanisms of susceptibility remain poorly understood. In this study, we performed longitudinal serum proteomic profiling of high-lesion (HL; lesion-susceptible) and no-lesion (NL; lesion-resistant) cattle (n = 5 per group per time point) at baseline, after lesion development, and following an antigen challenge stage using data-independent acquisition mass spectrometry. Using MSstats linear mixed-effects modelling with Benjamini-Hochberg correction (adjusted P < 1 × 10⁻⁵), we identified 149, 146, and 162 differentially abundant proteins (DAPs) at baseline, post-lesion, and post-challenge stages, respectively. At baseline, NL cattle exhibited higher levels of proteins involved in the immune response, such as complement factors, immunoglobulins, and mannose-binding lectin, suggesting a robust immune system. Lesion formation in HL cattle was accompanied by marked increases in acute-phase proteins and coagulation factors, indicating a strong inflammatory and procoagulant response. Following antigen challenge, NL cattle displayed enrichment of antioxidant and immune-regulatory proteins. These findings highlight candidate serum biomarkers associated with susceptibility to buffalo fly-related skin lesions.