Bovine respiratory disease (BRD) is the most common disease in beef cattle and leads to considerable economic losses in both beef and dairy cattle. It is important to uncover the molecular mechanisms underlying BRD and to identify biomarkers for early identification of BRD cattle in order to address its impact on production and welfare. In this study, a longitudinal transcriptomic analysis was conducted using blood samples collected from 24 beef cattle at three production stages in the feedlot: 1) arrival (Entry group); 2) when identified as sick (diagnosed as BRD) and separated for treatment (Pulled); 3) prior to marketing (Close-out, representing healthy animals). Expressed genes were significantly different in the same animal among Entry, Pulled and Close-out stages (false discovery rate (FDR) < 0.01 & |Fold Change| > 2). Beef steers at both Entry and Pulled stages presented obvious difference in GO terms (FDR < 0.05) and affected biological functions (FDR < 0.05 & |Z-score| > 2) when compared with animals at Close-out. However, no significant functional difference was observed between Entry and Pulled animals. The interferon signaling pathway showed the most significant difference between animals at Entry/Pulled and Close-out stages (P < .001 & |Z-score| > 2), suggesting the animals initiated antiviral responses at an early stage of infection. Six key genes including IFI6, IFIT3, ISG15, MX1, and OAS2 were identified as biomarkers to predict and recognize sick cattle at Entry. A gene module with 169 co-expressed genes obtained from WGCNA analysis was most positively correlated (R = 0.59, P = 6E-08) with sickness, which was regulated by 11 transcription factors. Our findings provide an initial understanding of the BRD infection process in the field and suggests a subset of novel marker genes for identifying BRD in cattle at an early stage of infection.

牛呼吸系统疾病（BRD）是肉牛最常见的疾病，给肉牛和奶牛都造成相当大的经济损失。重要的是要揭示 BRD 背后的分子机制，并确定用于早期识别 BRD 牛的生物标志物，以解决其对生产和福利的影响。在这项研究中，使用从饲养场三个生产阶段收集的 24 头肉牛的血液样本进行了纵向转录组学分析：1）到达（进入组）；2）当被确定为生病（诊断为BRD）并被隔离治疗（Pulled）时；3) 上市前（平仓，代表健康动物）。同一动物在进入、拉出和关闭阶段中表达的基因有显着差异（错误发现率 (FDR) < 0.01 & |Fold Change| > 2）。Z-分数| > 2) 与关闭时的动物相比。然而，在进入和拉动动物之间没有观察到显着的功能差异。干扰素信号通路在进入/拉出和关闭阶段显示出动物之间最显着的差异 ( P  < .001 & | Z -score| > 2)，表明动物在感染的早期阶段就开始了抗病毒反应。包括IFI6、IFIT3、ISG15、MX1和OAS2在内的六个关键基因被鉴定为生物标志物，用于预测和识别进入病牛。从 WGCNA 分析中获得的具有 169 个共表达基因的基因模块是最正相关的（R = 0.59, P  = 6E-08) 患病，受 11 个转录因子调控。我们的研究结果提供了对该领域 BRD 感染过程的初步了解，并提出了一组新的标记基因，用于在感染早期识别牛的 BRD。