Alveoli collapse leading to respiratory failure is one of the major causes of death in newborn cloned calves.The present study focused on the expression pattern of transcriptome in collapsed lung tissues and their relationship with neonatal respiratory distress syndrome (NRDS) in cloned calves.Bovine Gene Expression Microarray (Agilent, 4x44k, 43,803 probes) were used to identify different expression patterns of transcriptome in collapsed lung tissue from 4 newborn cloned calves with NRDS and normal lung tissues from 4 age-matched healthy individuals.Lung tissues were collected by dissection from newborns that died due to NRDS and from healthy individuals on the first day after birth.Totally,17418 transcripts were identified,including mRNA and lncRNA.1901 transcripts were up-regulated and 1605 transcripts were down-regulated in collapsed lungs of neonatal cloned cattle(p<0.05).The differentially expressed (DE) genes were enriched in 87 pathways (p<0.05) and 1040 GOs (p<0.05).Gene ontological analysis indicated that the DE genes were concentrated in the function of DNA-dependent regulation of transcription,transcription factor activity, protein phosphorylation etc.Interestingly, the lncRNA XIST were found significantly down regulated in collapsed lungs (p<0.05, fold change>2).The lack of XIST transcript may give rise to defective cell reprogramming of cloned cattle.The abnormal transcriptional pattern may contribute to the dysregulation of alveolus development leading to alveoli collapse and RDS.This project was supported by the National Natural Science Foundation of China (Grant No.31301977).