Dear Dr. Hu,

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

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Reviewer #1: In the ms. entitled ”Transcriptomic analysis reveals the impact of concurrent, resistance, and endurance training on skeletal muscle”, Zhao and co-workers have taken a transcriptomic approach to unravel common and separate transcriptomic mechanisms underlying different modes of physical training. It is shown that extracellular matrix remodeling is common to concurrent, resistance, and endurance training while distinct training-specific differences were also observed in gene expression between the three modes of training.

General comments: This is an interesting and ambitious approach to unravel differences in the gene expression response to three different modes of physical exercise regimes. In study limitations it is advised that changes in gene expression give important information on changes at the mRNA level which need to be translated to the protein level. In addition, there are other concerns which need to be addressed (see specific comments below).

Specific comments: The subjects participating in the study need to be described in more detail (age, body weight, height, baseline training status etc).

Concurrent, resistance and endurance training mean different for different people and these types of trainings need to be presented in detail.

The response to the different training regimes should be presented such as changes in body weight, strength and maximal oxygen uptake.

Minor comment: As mentioned at the end of the Discussion in study limitations, transcriptomics are associated with numerous limitations in the analyses of muscle fiber type transitions in response to e.g. physical exercise. However, enzyme-histochemical stainings are also associated with significant limitations. It is suggested that histochemistry is replaced by biochemical analyses of myosin isoform expression.

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Reviewer #1: No

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To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

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Transcriptomic Analysis Reveals the Impact of Concurrent, Resistance, and Endurance Training on Skeletal Muscle

PONE-D-25-54953R1

Dear Dr. Hu,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Donald Gullberg, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

An editor has reviewed the revised version and finds that the MS is a well written and interesting study of the effects of training on muscle gene transcription. The study opens up for more empirically based studies where gene expression in different cell types in different microenvironmental niches are studied in more detail.

Reviewers' comments: