Large-scale landscape of porcine respiratory disease complex–associated pathogens in Spanish swine production

The porcine respiratory disease complex (PRDC) poses a significant economic burden on global swine production and adversely impacts animal health and welfare due to its multifactorial nature and complex pathogen interactions. Here, through a comprehensive retrospective observational analysis of 6,017 routine diagnostic submissions from Spanish commercial swine farms (2020-2024) with suspected respiratory disease, we evaluated the frequency and co-detection patterns of 12 key PRDC bacterial and viral pathogens. Our results revealed marked geographic, temporal, and production-stage variations. Glaesserella (G.) parasuis (56.7%), Streptococcus (S.) suis (56.4%), porcine reproductive and respiratory syndrome virus-1 (PRRSV-1) (52.4%), and Mesomycoplasma (M.) hyorhinis (47.8%) were the most frequently detected agents. Notably, the frequency of these secondary opportunists rose steadily until 2022 before decreasing in the following years, mirroring declines in primary PRDC pathogens such as PCV2 and Mesomycoplasma (M.) hyopneumoniae. Secondary opportunistic bacteria were predominantly detected in post-weaning piglets (p < 0.05), while PRRSV-1 exhibited marked regional differences, with higher positivity in northeastern Spain (p < 0.05). Over 800 distinct co-detection patterns were identified, reflecting the complexity of pathogen combinations. Co-occurrence networks and logistic regression analyses underscored robust associations. Remarkably, M. hyorhinis emerged as a pivotal pathogen, showing strong links with nine of the evaluated pathogens, including G. parasuis (OR = 4.05), S. suis (OR = 1.57), and PRRSV-1 (OR = 2.55). These findings provide a large-scale, real-world overview of PRDC-associated pathogen detection and co-detection patterns, supporting evidence-based diagnostic and prevention priorities in commercial pig production. Together, they reinforce the need for integrated approaches to reduce the multifactorial burden of respiratory disease in swine.