<p>GO and KEGG analysis list of downregulated genes.</p>

Functional pathway enrichment analysis revealed significant alterations in immune and metabolic processes associated with SLD pathophysiology. Infected chickens exhibited significant activation of immune response pathways, particularly cytokine-cytokine receptor interactions involving interleukins <i>IL-22, IL-21,</i> and <i>IL-6,</i> along with enhanced cell signaling, and cell adhesion. Among the individual genes, <i>C1QTNF1</i> and the adhesion molecule gene <i>ADGRD1</i> were notably overexpressed, indicating enhanced inflammatory activity.

In contrast, core hepatic metabolic functions were profoundly reduced (adjusted p < 0.05) as evidenced by downregulation of oxidative phosphorylation, fatty acid metabolism, iron ion binding, and heme binding pathways. A marked increase in serum amyloid A (<i>SAA</i>) gene expression further indicated robust acute-phase responses and compromised liver function during infection. Together, these findings demonstrate a complex interplay between inflammatory activation and metabolic dysregulation during SLD.

The strong upregulation of acute-phase proteins and pro-inflammatory cytokines demonstrates the host’s vigorous attempt to combat bacterial infection, whereas the concurrent suppression of essential metabolic pathways reflects the pathological consequences of SLD. This study provides a transcriptomic characterization of host responses to <i>C. hepaticus</i> infection, offering insights into SLD pathogenesis and potential avenues for targeted intervention.</p></div>