Respiratory coronaviruses cause serious health threats to humans and animals. Porcine respiratory coronavirus (PRCV) is a natural variant of transmissible gastroenteritis virus (TGEV) with partial spike deletion, which causes mild respiratory disease. Despite antigenically similar, PRCV and TGEV differ significantly in tissue tropismTissue tropism and disease manifestations. As with several human coronaviruses, PRCV largely replicates in the epithelial cells of the nasal mucosa, trachea, bronchi, and bronchiole, resulting in mild respiratory disease or asymptomatic. PRCV provides a unique animal model for the study of human coronavirus respiratory disease given the fact that the anatomy, physiology, and immune system of the porcine respiratory tract closely resemble those of humans. An understanding of PRCV infections in the natural host is critical to provide insights into common and distinctive innate immunity related to human respiratory coronavirus infection. Additionally, the emergence of PRCV reduces the prevalence of TGEV in pork herds due to cross-protective immunity with TGEV. Therefore, PRCV is also an intriguing model for investigating the contributions of respiratory versus gastrointestinal mucosal immunity to local protection.