Author ORCID Identifier

https://orcid.org/0009-0005-3143-1844

Semester

Summer

Date of Graduation

2026

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Animal and Nutritional Sciences

Committee Chair

Ibukun Ogunade

Committee Member

Scott Bowdridge

Committee Member

Jianbo Yao

Committee Member

Joseph Lynch

Abstract

To meet the demands of the growing population, it is imperative to develop sustainable and applicable ways to improve animal health and productivity. The first step in doing so is understanding the mechanisms that govern health and immune response and find ways to appropriately modulate them to improve animal health and productivity. The objective of this study is to use multi-omic techniques to understand breed-specific immune responses in sheep that may contribute to their resistance and susceptibility to parasites and to a greater extent, immunocompetence. Known parasite-resistant breed, St. Croix (STC) were compared to parasite susceptible Suffolk (SUF) sheep for their hepatic metabolome and transcriptome response before lipopolysaccharide (LPS) administration, HR0, as well as 2 hours (HR2)and 6 hours (HR6) post administration. At HR0, metabolome data revealed 39 differentially abundant metabolites (AUC = 1; P ≤ 0.01) and 8 altered pathways (P ≤ 0.05) between STC and SUF. Of these metabolites, 33 were lower in  STC compared to SUF. At HR2, 36 differentially abundant metabolites (AUC = 1; P ≤ 0.01) and 10 altered pathways (P ≤ 0.05) were identified between STC and SUF. A total of 28 differentially abundant metabolites (AUC = 1; P ≤ 0.01) and only 2 altered pathways (P ≤ 0.05) were identified between STC and SUF at HR6. Transcriptomic data for the same animals at baseline (HR0) revealed upregulation of 141 differentially expressed genes (DEGs) between the breeds, most related to immune readiness, including innate immune response and defense response. HR2 responses showed almost double the DEGs in SUF compared to STC, most of which were similar, but to a greater magnitude than displayed in STC. Finally, at HR6, there was a similar amount of DEGs, however, STC sheep shifted from an immunity-related response to metabolic processes. Multi-omic assessment of immune responses suggests a greater magnitude of innate immune response in STC that shifted to faster metabolic recovery by hour 6. SUF displayed a more prolonged and heightened immune activity, suggesting a less effective resolution of the LPS-induced challenge. To further identify the connection between parasite resistance and immune competence, we evaluated the immune response of Katahdin sheep with divergent post-weaning fecal egg count (PFEC) estimated breeding values (EBV). Isolated post-mononuclear blood cells (PBMCs) from 10 Katahdin ewes (5 LoKat and 5 HiKat) were stimulated with lipopolysaccharide (LPS). RNA was extracted from stimulated cells and subjected to RNA-sequencing and further analyzed for DEGs. Between HiKAT control (HiKatCon) and treatment group (HiKatLPS) , a total of 354 DEGs were identified and pathway enrichment analysis revealed pathways mostly associated with cytokine production, regulation of cytokine production and positive regulation of cytokine production. Conversely, there were 162 DEGs for LoKatLPS compared to LoKatCON and the most enriched pathways were associated with adaptive immune response, positive regulation of response to stimulus and adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains. Results indicate the significant difference in the magnitude of response between LoKat and HiKat, despite both groups’ ability to respond to immunological stimuli. This study provides valuable insight into the application of multi-omic techniques to better understand the interconnectedness of parasite resistance and immunocompetence.

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