Physiological and Transcriptomic Basis of Disease Tolerance in Trypanotolerant N’Dama Cattle Versus Susceptible Zebu Cattle in Adamawa State, North East Nigeria

Disease tolerance, defined as the ability to maintain productivity despite parasite burden, is the defining feature of N'Dama cattle in trypanosome-endemic regions, yet its physiological and transcriptomic foundations in the North East Nigerian context have not been investigated through a comparative cross-species molecular approach. This doctoral study characterised the physiological and transcriptomic basis of trypanotolerance in N'Dama cattle versus susceptible Zebu cattle in Adamawa State, North East Nigeria, making original contributions to understanding of the tolerance-resistance distinction in bovine trypanosomiasis. Sixty N'Dama and sixty Zebu cattle were subjected to standardised experimental Trypanosoma brucei brucei infection under biosafety-controlled conditions. Haematological, biochemical, metabolomic, and whole blood transcriptomic analyses were conducted at days zero, fourteen, twenty-eight, and fifty-six post-infection. Physiological tolerance in N'Dama manifested as maintenance of haemoglobin above 8 g/dL and body weight stability despite parasitaemia levels not significantly lower than Zebu cattle. Transcriptomic analysis revealed 312 differentially expressed genes in N'Dama versus Zebu at peak parasitaemia. Upregulated pathways in N'Dama included erythropoiesis, anti-apoptotic signalling in erythroid precursors, and nuclear factor erythroid 2-related factor 2-driven antioxidant gene networks. Zebu showed dominant upregulation of inflammatory cytokine cascades without corresponding erythropoietic compensation. Metabolomics confirmed superior antioxidant metabolite availability in N'Dama. This doctoral study provides an original multi-omics mechanistic distinction between tolerance and susceptibility in bovine trypanosomiasis and advances theoretical frameworks for tolerance-based breeding and pharmaceutical strategies in North East Nigeria. Keywords: trypanotolerance, N'Dama cattle, transcriptomics, disease tolerance, Trypanosoma brucei.