Mannheimia haemolytica (Mh) is a major bovine respiratory pathogen that can trigger marked inflammatory and barrier injuries. This study evaluated the protective effect of oral curcumin pretreatment in a proof-of-concept mouse model of early Mh-induced acute pulmonary injury. Mice received curcumin at 50 or 150 mg/kg/day for seven days before an intranasal Mh challenge and were evaluated 12 h after infection. Curcumin pretreatment was associated with lower lung wet-to-dry ratios, bronchoalveolar lavage fluid protein concentrations, histological injury scores, and serum pro-inflammatory cytokine levels. It was also associated with reduced abundance or phosphorylation of NF-κB/NLRP3-related proteins, increased expression of Nrf2-associated antioxidant proteins, reduced apoptosis, and preservation of the tight-junction protein ZO-1. In addition, curcumin pretreatment was associated with changes in fecal microbial composition and intestinal short-chain fatty acid profiles, including partial recovery of propionic acid. Because this study did not include a curcumin-only group, post-infection treatment, bacterial-burden measurements, pathway-perturbation experiments, or microbiota-causality experiments, the findings support prophylactic host-protective associations in an early mouse model rather than antibacterial activity, therapeutic efficacy after established infection, or causal gut–lung mechanisms. Validation in bovine models is required before veterinary application.